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Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells. [ABSTRACT FROM AUTHOR]

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)‐cells have recently gained much attention. We performed an in‐deep phenotypic analysis of NK‐cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty‐seven PLWH (22 long‐term EC [PLWH‐long‐term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH‐onART], and 10 noncontrollers cART‐naïve [PLWH‐offART]), and 20 uninfected controls were included. NK‐cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK‐cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK‐cells clusters based on the expression levels of the 15 different markers. PLWH‐offART presented the highest disturbance of NK‐cells homeostasis and this was not completely restored by long‐term ART. Interestingly, long term spontaneous control of HIV (PLWH‐LTEC group) was associated with a specific profile of NK‐cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p‐value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p‐value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long‐term control of HIV. [ABSTRACT FROM AUTHOR]

Aims: Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. Methods and results: Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high‐sensitivity C‐reactive protein, and N‐terminal‐pro‐brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow‐up was 5.44 (3.03–7.46) years. Two hundred and ninety‐four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08–1.29], P < 0.001), calcidiol (HR 0.86 [0.74–1.00], P = 0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28–1.65], P < 0.001) and parathormone (HR 1.06 1.01–1.12]; P = 0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07–1.37], P = 0.002) and calcidiol (HR 0.72 [0.54–0.97), P = 0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Conclusions: FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Ample evidence indicates a sex‐related difference in severity of COVID‐19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID‐19 severity. Objective: To test the association between the androgen receptor polyQ polymorphism and COVID‐19 severity in a large cohort of COVID‐19 male patients. Materials and methods: This study included 1136 male patients infected with SARS‐CoV‐2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID‐19 severity was assessed by Chi‐squared (Chi2) and logistic regression analysis. Results: The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). Discussion: Androgen sensitivity may be a critical factor in COVID‐19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID‐19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID‐19 outcome. Conclusions: The results obtained in our study do not support the role of this polymorphism as biomarker of COVID‐19 severity. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF. Methods Nine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2nd edition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100). Results The age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32). Conclusions Disability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.

Because of their intrinsic properties, carbon nanotubes (CNTs) have been suggested for biomedical applications. We studied the anti-adherent performance of two ultra-high-molecular-weight polyethylene (UHMWPE) surfaces which contains 3% multi-wall CNT variant (MWCNT): Nanocyl/UHMWPE and Arc/ UHMWPE. These surfaces were obtained by hot pressure forming after mechanical mixture. Additional nanoindentation studies were performed and hardness and stiffness were determined. Mechanical properties of the MWCNT/UHMWPE composites were also compared to raw UHMWPE and correlated with their anti-adherent performance. Comparing with UHMWPE, Nanocyl/UHMWPE was the least adherent surface. Bacterial adherence was also significantly reduced in Arc/UHMWPE for four strains. [ABSTRACT FROM AUTHOR]